An open-label, multicenter, adaptive, phase Ib/II study of QL1706 or QL1604 plus bevacizumab as first-line treatment in patients with advanced hepatocellular carcinoma.
Authors: Feng Bi, Yan-qiao Zhang, Shanzhi Gu, Yabing Guo, Zhongyuan Xu, Hao Ying, Mingxu Da, Chaoying Liu, Yaozhen Pan, Yao Huang, Zhiyu Chen, Zheng Wang, Jianbing Wu, Shangeng Weng, Yanjun Wang, Jun Zhao, Xiaokui Yu, Hui Li, Shilin Xue, Xiaoyan Kang
Journal: Journal of Clinical Oncology (2023)

4077 Background: Cancer immunotherapy has expanded the treatment options for advanced HCC (aHCC). Atezolizumab plus bevacizumab is approved as the standard of care for patients (pts) with aHCC. QL1706 is a novel dual immune checkpoint blockade containing a mixture of anti-PD-1 IgG4 and anti-CTLA4 IgG1 antibodies (Abs). QL1604 is a humanized mAb against PD-1. The anti-PD-1 Ab of QL1706 has the same protein sequence and was produced by using the same single clone selection method with QL1604. Here we report the safety and efficacy results from a Ph Ib/II study of QL1706 or QL1604 plus bevacizumab (beva) as first-line treatment in pts with aHCC. Methods: Eligible pts had histologically or clinically confirmed HCC; had BCLC stage B/C disease and Child-Pugh class A and B liver function; were systemic therapy naive; and were not suitable for radical surgery and/or locoregional therapy, or progressed after surgery and/or locoregional therapy. This study included 3 parts. Part 1 included a safety run-in phase and an expansion phase. Patients were enrolled to receive QL1706 5 mg/kg plus beva 15 mg/kg Q3W. In part 2, pts were randomized to receive QL1604 200 mg or QL1706 5 mg/kg plus beva 15 mg/kg Q3W. In part 3, pts were enrolled to receive QL1706 7.5 mg/kg plus beva 15 mg/kg Q3W. Initiation of part 3 was to be determined based on factorial analysis on the results from parts 1 and 2. Each treatment cycle lasted for 21 days. Treatment continued until disease progression or other discontinuation events. The primary endpoint was safety. Secondary endpoints included efficacy etc. Results: As of data cutoff (18 Nov 2022), 76 pts were enrolled in parts 1 and 2 (QL1706: 50; QL1604: 26). The baseline characteristics were balanced between the 2 groups. A total of 43 (86%) pts and 23 (88.5%) pts in QL1706 and QL1604 groups experienced TRAEs. For both groups (QL1706 vs QL1604), the most common TRAEs were platelet count decreased (26% vs 23.1%); followed by AST increased (22% vs 19.2%). A total of 17 (34%) pts and 10 (38.5%) pts in QL1706 and QL1604 groups experienced Gr≥3 TRAEs. A total of 25 (50%) pts and 5 (19.2%) pts in QL1706 and QL1604 groups experienced irAEs. The most common irAE in the QL1706 group was rash (16%) (vs 3.8% for QL1604). A total of 8 (16%) pts and 6 (23.1%) pts in QL1706 and QL1604 groups experienced TRSAEs. In the efficacy evaluable population, the ORR was 38.3% (18/47) and 15.4% (4/26) in QL1706 and QL1604 groups. The DCR was 74.5% and 69.2% in QL1706 and QL1604 groups. The mPFS was 6.7 months (95% CI: 3.0-11.4) and 5.4 months (95% CI:2.4-8.5) in QL1706 and QL1604 groups. The mOS was not reached. Conclusions: QL1706 5 mg/kg showed comparable safety profile and numerically higher ORR and longer mPFS vs QL1604 when combined with beva as first-line treatment in pts with aHCC. Ph III head-to-head clinical trial to compare QL1706 or anti-PD-1/PD-L1 Ab plus beva in this population has been planned. Clinical trial information: NCT05603039 .